A rare genetic mutation which is inherited through families can increase the risk of developing lung cancer 25-fold, according to a new study.
The research led by researchers at Dana Farber Cancer Institute in Boston, MA and the 23andMe research institute looked at data from 3.3 million people who had consented to have their 23andMe genetic information used for research. The work, published in found that people who carried a specific mutation in the EGFR gene known as T790M had a hugely inflated risk of developing lung cancer.
“Today, lung cancer screening is driven almost entirely by smoking history,” said Jaclyn LoPiccolo, MD, PhD, attending physician and lung cancer researcher at Dana-Farber Cancer Institute, who co-led the study.” Our findings raise the possibility that, in the future, screening could also be dictated by inherited genetic risk.”
The mutation is not the first heritable genetic risk factor for lung cancer, but it appears to have the strongest impact on risk of any identified so far.
“Other inherited cancer-predisposition genes, including TP53, BRCA2 and ATM, have also been associated with increased lung cancer risk. What is unusual about germline EGFR T790M is the magnitude of the risk and its specificity to lung cancer,” said Dr LoPiccolo.
Many genetic mutations increase the risk of multiple different types of cancer, including those in BRCA1 and 2, which predispose carriers to breast, ovarian, prostate and pancreatic cancers among others. But EGFR T790M carriers seemed to only have an increased risk of developing lung cancer.
“In our study, a single inherited mutation was associated with approximately 25-fold higher odds of lung cancer, without evidence of increased risk for the other 17 cancers we examined,” said Dr LoPiccolo.
The mutation was discovered in 2005 in a family with several cases of lung cancer and other families with EGFR T790M mutations have since been studied. But until now, there haven’t been enough documented cases for researchers to figure out how much of a strong cancer predisposition factor the mutation is.
People who smoke tobacco products already have a significant lifetime chance of developing lung cancer, but in people who carried the mutation, this risk was ten times higher than in those who didn’t carry the mutation. Among people who had never smoked, people with the mutation were 60 times as likely to develop lung cancer. This does not mean that non-smokers with the mutation have a higher overall risk than smokers with the mutation, because smoking itself substantially increases lung cancer risk.
Most lung cancer cases are associated with the use of tobacco products and sometimes ,but lung cancer also occurs increasingly or have an obvious link to other significant risk factors. Researchers globally are still trying to figure out why many of these cases occur and this new research suggests that at least some of them might be due to this inherited genetic variant.
The variant is rare, found in only approximately 1 in 16,000 people in the study, but if there is a lot of lung cancer cases in someone’s family, especially in non-smokers, or at young ages it might be worth seeking testing and professional advice.
“Ultimately, if someone is concerned that they may carry this mutation, or have a family member who carries this mutation, the best next step is to discuss it with a genetics professional, or their oncologist, if they have one,” said Dr LoPiccolo, mentioning that there is an ongoing study called open to participants across the United States who are likely to have an inherited higher risk of developing lung cancers. “Through INHERIT, we are studying inherited risk for lung cancer and piloting CT screening in people who carry T790M,” said Dr LoPiccolo.
There is currently no way to prevent lung cancer in people carrying the EGFR T790M mutation, but not smoking and undergoing screening to identify any cancer early will increase the chances of successful treatment if cancer does develop.
“Avoiding tobacco exposure is the biggest thing someone can do to reduce their risk, although we know that these cancers can also occur in people who have never smoked. Right now, our major opportunity is early detection through CT scans, in efforts to find lung cancer at its most curable stages,” said Dr LoPiccolo.